Test structures consisting of shallow trench isolation ~ STI ! structures are fabricated using advanced silicon ~ Si ! technology. Different process parameters and geometrical features are implemented to investigate the residual mechanical stress in the structures. A technology computer aided design homemade tool, IMPACT, is upgraded and optimized to yield strain fields in deep submicron complementary metal–oxide–semiconductor devices. Residual strain in the silicon substrate is measured with micro-Raman spectroscopy ~m -RS ! and/or convergent beam electron diffraction ~ CBED ! for large ~ 25 m m ! and medium size ~ 2 m m ! , while only CBED is used for deep submicron STI ~ 0.22 m m ! . We propose a methodology combining CBED and technology computer aided design ~ TCAD ! with m -RS to assess the accuracy of the CBED measurements and TCAD calculations on the widest structures. The method is extended to measure ~ by CBED ! and calculate ~ by TCAD ! the strain
The discovery of novel antihelmintic molecules to combat the development and spread of schistosomiasis, a disease caused by several Schistosoma flatworm species, mobilizes significant research efforts worldwide. With a limited number of biochemical assays for measuring the viability of adult worms, the antischistosomicidal activity of molecules is usually evaluated by a microscopic observation of worm mobility and/or integrity upon drug exposure. Even if these phenotypical assays enable multiple parameters analysis, they are often conducted during several days and need to be associated with image-based analysis to minimized subjectivity. We describe here a self-purifying microfluidic system enabling the selection of healthy adult worms and the identification of molecules acting instantly on the parasite. The worms are assayed in a dynamic environment that eliminates unhealthy worms that cannot attach firmly to the chip walls prior to being exposed to the drug. The detachment of the worms is also used as second step readout for identifying active compounds. We have validated this new fluidic screening approach using the two major antihelmintic drugs, praziquantel and artemisinin. The reported dynamic system is simple to produce and to parallelize. Importantly, it enables a quick and sensitive detection of antischistosomal compounds in no more than one hour.
This article aims to show the influence of surface characteristics (microtopography, chemistry, mechanical properties) and seawater parameters on the settlement of marine micro- and macroorganisms. Polymers with nine microtopographies, three distinct mechanical properties, and wetting characteristics are immersed for one month into two contrasting coastal sites (Toulon and Kristineberg Center) and seasons (Winter and Summer). Influence of microtopography and chemistry on wetting is assessed through static contact angle and captive air bubble measurements over 3-weeks immersion in artificial seawater. Microscopic analysis, quantitative flow cytometry, metabarcoding based on the ribulose biphosphate carboxylase (rbcL) gene amplification, and sequencing are performed to characterize the settled microorganisms. Quantification of macrofoulers is done by evaluating the surface coverage and the type of organism. It is found that for long static in situ immersion, mechanical properties and non-evolutive wettability have no major influence on both abundance and diversity of biofouling assemblages, regardless of the type of organisms. The apparent contradiction with previous results, based on model organisms, may be due to the huge diversity of marine environments, both in terms of taxa and their size. Evolutive wetting properties with wetting switching back and forth over time have shown to strongly reduce the colonization by macrofoulers.
Schistosomiasis is a challenging parasitic model due to the absence of transgenic strains and systems allowing maintenance of heathy worms outside of their host (mammals). Classical in vitro studies (Petri dish) do not allow long-term survival of worm couples with retention of basic biological functions like mobility and pairing. We have designed a microfluidic device that sustainably cultivates adult worm couples. The influences of the composition and physical characteristics of mass flow on the mobility, pairing and long-term survival of worms have been studied. We have also assessed the effect of Praziquantel, the only therapeutic molecule currently in use.
Pancreatic cancer (PC) is a deadly cancer for which no diagnostic or prevention plan currently exists since this cancer is asymptomatic in its early development. The very specific and complex tumor microenvironment of PC is responsible for the unsuccessful delivery of therapeutics molecules to tumor cells. For high throughput testing of new molecules, there is a crucial need for more accurate preclinical model. For the first time, we integrated in a microfluidic system 5 major features of PC microenvironment: i) type-I collagen (CI), ii) hyaluronic acid (HA), iii) pancreatic stellate cells (SC), iv) interstitial fluid flow and v) nutrient and oxygen gradients. We showed long 3D culture (30 days). Furthermore, we implemented, thanks to the perfusion capability, the actual FOLFIRINOX protocol to assess the IC50 and we showed that dynamic conditions induce increased chemoresistance compared to 3D static.
Ex vivo explant culture models offer unique properties to study complex mechanisms underlying tissue growth, renewal, and disease. A major weakness is the short viability depending on the biopsy origin and preparation protocol. We describe an interphase microfluidic culture system to cultivate full thickness murine colon explants which keeps morphological structures of the tissue up to 192 h. The system was composed of a central well on top of a porous membrane supported by a microchannel structure. The microfluidic perfusion allowed bathing the serosal side while preventing immersion of the villi. After eight days, up to 33% of the samples displayed no histological abnormalities. Numerical simulation of the transport of oxygen and glucose provided technical solutions to improve the functionality of the microdevice.
Lignin is the second most abundant polymer after cellulose in lignocellulosic biomass. Its aromatic composition and recalcitrant nature make its valorization a major challenge for obtaining low molecular weight aromatics compounds with high value-added from the enzymatic depolymerization of industrial lignins. The oxidation reaction of lignin polymer using laccases alone remains inefficient. Therefore, researches are focused on the use of a laccase-mediator system (LMS) to facilitate enzymatic depolymerization. Until today, the LMS system was studied using water-soluble lignin only (commercial lignins, modified lignins, or lignin model compounds). This work reports a study of three LMS systems to depolymerize the three major industrial lignins (organosolv lignin, Kraft lignin, and sodium lignosulfonate). We show that an enzymatic depolymerization of these lignins can be achieved by LMS using laccase from Trametes versicolor, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt as mediator and a cosolvent (25% of 1,4-dioxane) to enhance the solubilization of lignins.
We have investigated, theoretically using finite difference time domain method, and experimentally using Fourier transform infrared spectroscopy, the effect of grating's parameters on the reflective properties of ridges and holes' photonic crystal membrane made of polycrystalline silicon in the mid-infrared (MIR) range (5-15 mu m). We found that the interaction of an incident wave with the ridges and the drilled membrane modifies the reflective spectrum in a similar way. For the two geometries we first found Fabry-Perot effect due to the variation of the effective index of the membrane. Then, in both cases, we have been able to highlight the occurrence of dips in the reflection spectrum which are due to the structuration of the membrane. We showed that for the ridge structure, the mode is confined inside the ridges while for the drilled layer, the mode is spread over the whole membrane. Reflectivity tuning in the MIR frequency range can be achieved and we have calculated that the reflectivity of the photonic membrane can be modulated from 20% to at least 40%. It opens new perspectives in the fields of thermal insulation of buildings, high reflective optical mirrors and coatings and personal thermal management.
Coupling electrohydrodynamic forces and electrowetting-on-dielectric actuation allows concentration of diluted biological samples in 10 μL droplets.
Known for its electric properties, poly (3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) has emerged as a good candidate for organic electronics and more recently for bio-applications. Despite its growing use in engineering applications, little is known about the stability in time of its interface properties. Here, we consider the surface ageing of PEDOT:PSS when it is stored in environments with various relative humidity and temperature conditions and as a function of the cross-linking agent's (3-glycidoxypropyltrimethoxysilane) concentration. Our systematic wettability study over 6 months reveals that the PEDOT:PSS interface undergoes significant reorganization and some irreversible changes on these timescales regardless of the concentration of cross-linker added.
One of the promising strategies to achieve high performance flexible electronics is to integrate high performance components (micro-electro-mechanical systems, integrated circuit, etc.) on a flexible substrate. The heterointegration of fragile high performance components, for example, thinned down 100 GHz silicon technology, necessitate however methodologies to place these components on the substrate while exerting as little force as possible to prevent any damage from occurring. In this work, a novel approach is presented for component positioning by capillary assembly on a smart flexible substrate composed of two layers of polymers. It is shown how the wettability of the surface can be engineered by combining stretching induced deformation of the top layer with plasma treatment. Using magnetically actuated ferrofluid droplets which carry the silicon chip shows how it can be aligned and deposited at predetermined sites on these substrates. It is demonstrated that unlike standard capillary alignment which relies on a hydrophobic/hydrophilic contrast, in this case deposition is controlled by surface adhesion contrast between the site and the rest of the substrate. Furthermore, it is explained how deposition sites can be selectively activated through localized stretching thus producing generic smart substrates on which precise depositions sites can be activated according to the needs of the end user.
In vitro models of the liver microvasculature, especially with respect to cancer cell extravasation, should include not only endothelial and cancer cells but also surrounding cells to mimic the physiological situation. To this end, in the present study, we established a physiologically-relevant hierarchical co-culture model by stacking layers of primary rat hepatocytes (Hep), hepatic stellate cells embedded in collagen gel (LX-2) and endothelial cells (HUVECs) on a specially designed oxygen-permeable polydimethylsiloxane PDMS bottom plate. The model was used to investigate the role and contribution of each of the three cell types in pancreatic cancer and promyeloblast cell adhesion. In particular, we showed an increase in albumin production by the primary hepatocytes and in the consumption of the produced vascular endothelial growth factors (VEGFs). Furthermore, in co-culture, the HUVECs exhibited a mature vascular endothelial and non-inflamed phenotype, as evidenced by Stabilin-1, lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1), intercellular adhesion molecule (ICAM-1), and vascular adhesion protein-1 (VAP-1) expression. The HUVECs were also successfully activated with an inflammatory cytokine and their ICAM-1 response was found to be higher in monoculture compared to co-culture. Additionally, the adhesion of MiaPaCa-2 pancreatic cancer cells and HL60 promyeloblasts was tested in both cases (i.e.: activation or not by an inflammatory cytokine). It has been found that their adhesion was always reduced in the co-culture model. These results highlight the importance of integrating hepatic stellate cells in the design of biomimetic models of the hepatic endothelial barrier.
Conducting polymers demonstrate an interesting ability to change their wettability at ultralow voltage (<1 V). While the conducting hydrogel poly(3,4-ethylenedioxythiophene) polystyrenesulfonate (PEDOT:PSS) is increasingly used as an interface with biology partly thanks to its mechanical properties, little is known about the electrical control of its wettability. We rely on the captive bubble technique to study this hydrogel property under relevant conditions (fully immerged). We here report that the wettability variations of PEDOT:PSS are driven by an electrowetting phenomenon in contrast to other conducting polymers which are thought to undergo wettability changes due to oxido-reduction reactions. In addition, we propose a modified electrowetting model to describe the wettability variations of PEDOT:PSS in aqueous solution under ultralow voltage and we show how these variations can be tuned in different ranges of contact angles (above or under 90°) by coating the PEDOT:PSS surface.
Cryptosporidium parvum is a major cause of diarrheal illness and was recently potentially associated with digestive carcinogenesis. Despite its impact on human health, Cryptosporidium pathogenesis remains poorly known, mainly due to the lack of a long-term culture method for this parasite. Thus, the aim of the present study was to develop a three-dimensional (3D) culture model from adult murine colon allowing biological investigations of the host-parasite interactions in an in vivo- like environment and, in particular, the development of parasite-induced neoplasia. Colonic explants were cultured and preserved ex vivo for 35 days and co-culturing was performed with C . parvum . Strikingly, the resulting system allowed the reproduction of neoplastic lesions in vitro at 27 days post-infection (PI), providing new evidence of the role of the parasite in the induction of carcinogenesis. This promising model could facilitate the study of host-pathogen interactions and the investigation of the process involved in Cryptosporidium -induced cell transformation.
In this study, we characterize the impact of electrical stimuli on the wettability and volume of thin films of poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) in aqueous solution. At low voltage (<;1V), we demonstrate a 20° to 30° modulation of the contact angle controlled by an electrowetting phenomenon and not by electrochemical reactions like usually seen for other common conducting polymers. Consequently, the contact angle range can be tuned by chemical functionalization of its interface. Besides, we show that the polymer presents a small swelling (<;4%) when the potential is turned from 0.2V to -0.8V. Finally, we develop fabrication processes to texture the PEDOT:PSS surface at microscale and nanoscale.
We present an experimental study of stick-jump (SJ) evaporation of strongly pinned nanoliter volume sessile water droplets drying on micropatterned surfaces. The evaporation is studied on surfaces composed of photolithographically micropatterned negative photoresist (SU-8). The micropatterning of the SU-8 enables circular, smooth, trough-like features to be formed which causes a very strong pinning of the three phase (liquid-vapor-solid) contact line of an evaporating droplet. This is ideal for studying SJ evaporation as it contains sequential constant contact radius (CCR) evaporation phases during droplet evaporation. The evaporation was studied in nonconfined conditions, and forced convection was not used. Micropatterned concentric circles were defined having an initial radius of 1000 μm decreasing by a spacing ranging from 500 to 50 μm. The droplet evaporates, successively pinning and depinning from circle to circle. For each pinning radius, the droplet contact angle and volume are observed to decrease quasi-linearly with time. The experimental average evaporation rates were found to decrease with decreasing pining radii. In contrast, the experimental average evaporation flux is found to increase with decreasing droplet radii. The data also demonstrate the influence of the initial contact angle on evaporation rate and flux. The data indicate that the total evaporation time of a droplet depends on the specific micropattern spacing and that the total evaporation time on micropatterned surfaces is always less than on flat, homogeneous surfaces. Although the surface patterning is observed to have little effect on the average droplet flux-indicating that the underlying evaporation physics is not significantly changed by the patterning-the total evaporation time is considerably modified by patterning, up to a factor or almost 2 compared to evaporation on a flat, homogeneous surface. The closely spaced concentric circle pinning maintains a large droplet radius and small contact angle from jump to jump; the result is a large evaporation rate leading to faster evaporation.
We have designed and fabricated a microfluidic system made of glass and polydimethylsiloxane. A micro-magnetometer has been integrated to the system. This sensor is made of a giant magneto-impedance wire known to have very high magnetic sensitivity at room temperature. A liquid-liquid segmented multiphase flow was generated in the channel using a Y-shaped inlet junction. The dispersed phase plugs contained superparamagnetic iron oxide (20 nm) nanoparticles at a molar concentration of 230 mmol/l. We have shown both theoretically and experimentally that in-flow detection of these nanoparticles is performed by the microsystem for concentration as small as 5.47 × 10−9 mol. These performances show that it is conceivable to use this system for ex-vivo analysis of blood samples where superparamagnetic iron oxide nanoparticles, initially used as magnetic contrast agents, could be functionalized for biomarkers fishing. It opens new perspectives in the context of personalized medicine.